Zinc is essential for human health. Marginal deficiency of zinc appears to be widespread but the diagnostic criteria for this have not been developed. Homeostatic control mechanisms at the gast-intestinal tract level during zinc deficiency and sufficiency are not well characterised in human subjects. The specific aims of this project are to define marginal zinc deficiency inhuman subjects and to determine homeostatic control mechanisms of zinc. These objectives will be accomplished by experimentally inducing a marginal specific deficiency of zinc in adult volunteers followed by appropriate repletion phases. The parameters of measurement of measurement will be: zince absorption, a measurement of mobile body zinc pool by using the novel method of stable isotopes (Inductively Coupled Plasma Mass Spectrometry (ICP/MS)), zinc balance, zinc concentration in plasma, red cells, neutrophils, lymphocytes, and saliva, assay of selected zinc- dependent enzymes in the plasma, red cells, lymphocytes, and neutrophils, dark adaptation, serum hormones, and lymphocyte funciton tests. A semi-purified diet based on texturized soy protein with different levels of zinc will be used for our study. All other macro and micro-nutrients will be supplied according to RDA. Throughout the experiment, the diet will remain constant except for zinc (3 mg/day during zinc-depletion phase and 30 mg/day during zinc-repletion phase). Alkaline phosphatease in the plasma, nucleoside phospyorylase and delata amino levulinic acid dehydratase in the red cells, alkaline phosphatase in the neutrophils (quantitative), and nucleoside phosphorylase and ecto 5' nucleotidase in the lymphocytes, will be determined and correlated with changes in zinc levels due to dietary manipulation. In vitro assessments of lymphocytefunctional activity (NK cell, IL-1, and IL-2 prodcution), surface markers, and cell culture studies will also be made. During the depletion- epletion phases for zinc, apprpriate measurements of gastro- intestinal absorption, zinc balance, and fecal loss of endogenously secreted zince will be carried out. Thus, these studies will provide us with sensitive criteria for making a diagnosis of marginal zinc deficiency and will provide homeostatic control mechanism of zinc at the gastro-intestinal level. Attempts will be made to develop monoclonal antibody to metallothioein by Hybridoma technique and set up ELSA technique for assay of this protein in plasma during the study. Intestinal secrtion of zinc will be determine by incubation studies.